A Review on Arsenic Toxicity Induced Keratosis and its Prevalence
Noor Ul Ain, Hamna Kaleem, Zahra Batool, Arbab Zafar, Khateeba Azmat, Ramish Karamat, Hiba Siddiqui, Zobia Sohail, Ruhma Iqbal, Mahnoor Younis
Department of Pharmacology, Government College University, Faisalabad 38000, Pakistan
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METADATA
Paper history Received: 2 Jan 2025 Revised: 27 February 2025 Accepted: 25 April 2025 Published online: 12 June 2025
Corresponding author Email: ananoorkhan105@gmail.com https://orcid.org/0000-0001-7085-2231 (Noor Ul Ain)
Keywords Arsenic Keratosis Hyperpigmentation Precancerous Lump
Citation Noor Ul Ain, Kaleem H, Batool Z, Zafar A, Azmat K, Karamat R, Siddiqui H, Zobia S, Iqbal R, Younis M (2025) A review on arsenic toxicity induced keratosis and its prevalence. Innovations in STEAM: Research & Education 3: 25030102. https://doi.org/10.37723/ISRE/0022.
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ABSTRACT
Background: Rapidly increasing discharge of arsenic (As) is a major health concern due to its cancer-causing effects. Excessive exposure of As causes the cancer of many organs including skin, liver, kidney, lungs. Precancerous skin condition due to the exposure of As is called As-keratosis, which is marked by hyperpigmentation and plaques and lump formation. The article focal point is the skin cancer which is the most concerning one. Methodology: This review was conducted by using major database including Google Scholar and PubMed. Review findings: Toxicity due to As is a global health related issue which affect people globally. As-keratosis is inveterate clinical or subclinical deadly harmful because of the presence of As metalloid in the body at higher level. A cross-sectional analysis was held to investigate the exposure of As is due to the number of reasons which includes contaminated water and sanitary landfills, etc. Diagnosis is based on the laboratory examination and histopathological examination. It is also diagnosed by the measuring the amount of As in blood, urine and hairs sample. Pathophysiology of the keratosis describe that the trivalent arsenide and methylation of As cause hyperpigmentation. Conclusion: For the prevention of As keratosis make sure the usage of As treatment plant for the availability of As free water for drinking purposes. Options for the treatment purpose include the use of the oral and topical medications and surgical excision. For the management of As keratosis nanotechnology use to remove As from ground water. |
INTRODUCTION
Contamination and the filthy pollutants caused due to Arsenic (As), which is a heavy metal is a universal considerable challenge, it becomes a major issue, a health hazard to humans who are being exposed to this heavy metal. As is known for its cancer-causing properties, called as King of poisons, which shows the acuteness of its toxicity (Li et al. 2025). As-keratosis is a precancerous causing skin cancer, pigmentation changes, and neurological changes by long-term chronic exposure to heavy metal. As is carcinogenic metalloid which is present in groundwater, soil, rock and air (Tao and Wang 2024). Due to high illiteracy rate and lack of knowledge among people living in such areas and being exposed through As poisoning and peak level of extremities of detrimental health related issues due to As by drinking such polluted water is ambiguous and inadequately evidenced, which carries a high risk of proceeding into cutaneous squamous cell carcinoma and can be represented with clinical and subclinical lesions (Ibrahim et al. 2006). Humans have had a very long, hysterical and chaotic relationship with heavy metals. Their prevalent nature and human’s dependency on heavy metals for production, have outgrowth consequences that causes systemic toxicity. In spite of clinical knowledge and related experience more than a decade ago, toxicity and poisoning effects caused due to heavy metals have now become representative and most problematic point of interest and perverted outcome in clinical toxicology is potentially fatal and it is a notion that is mainly and primarily aided by studies and performing experiments on animals and collecting data. Due to restricted research and experiments performed on animals may escalate the rate of heavy metal excretion, their curative effectiveness regards to morbidity and mortality is large (Kosnett 2010).
This
article scrutinizes the clinical exemplar and pathophysiology of As poisoning,
a heavy metal. The term “arsenic” is a derivative word from the Latin,
“Arsenicum”that usurp from a Syriac word “(al)zarniqa”,
which means “yellow orpiment”. Antecedently,
As is thought as a metalloid due to its dual properties such as they
consider to possess metallic and non-metallic characteristics, for time bein in accordance to the reference book of
toxicology, As accounts as a toxic
metal, which is translucent, odorless, and tasteless (Hall,
2002; Rajiv et al. 2023). As metal possess two compounds having chemical-valences of three and five. The chemical compound of As (As2O3), which
possess
tri-valent property, has high level of toxicity than the compound which is
penta-valent. As is metabolized by the
liver and excreted mainly through the kidneys about 90–95% (Sy,
Salud‐Gnilo et al. 2017). The purpose of this review
article was to synthesize an up-to-date knowledge of As induced keratosis
including its prevalence, diagnosis, treatment and prevention.
HEAVY METAL EXPOSURE
Exposure due to heavy metal and their core
root are natural sources and industrial
as well as medicinal. It can invade in
humans
through absorption, nasal route, and
ingestion. As contamination due to natural source involves soil,
water, rocks, of which the most common
is by drinking tap water comes from
underground sources (Lee 2017;
Demissie et al. 2023). Peak level of As metal stratum
was noticed and then reported in deep
aquifers. As can
endow
in industry for manufacturing
pesticides, dyes, HED, and semiconductors. It is suggested
that the surplus
As amount in cosmetic product’s preparation
should be within the specified limit
and must be less than 5 ppm (Tao
and Wang 2024). Research have proclaimed
that As is present in color pigments
used as a cosmetic product in eye-shadows, leads to dermatitis of eyelid and
even promote cancers of skin on its long-term use. As
metal is broadly
classified as and used in striated
medicinal preparations as
an ingredient of many
natural preparations, by use of herbs
and allopathic formulations,
in various diseases treatment such as
asthma, psoriasis, eczema, and Hodgkin’s disease,
leprosy, squamous cell carcinoma,
followed by long-term administration
of conventional medicinal therapy which
contains As metal for chronic psoriasis (Rajiv et
al. 2023).
KERATOSIS CAUSED BY ARSENIC
Keratosis
due to heavy metal As is a pre-malignant and venomous plague in
human beings
that shows chronic exposure due to As has become
an outgrowth effect
. Toxicity of As is the most acute and primitive bio
marker (Ganie
et al. 2024).
Lesions erupt
as firm, punctate, symmetric papules
corn-like in appearance fuse
to form scaly,
hyper pigmented, warts on skin (Huang et al. 2019; Table 1). They are
on areas of body which prone to produce
friction like soles of feet and palm of hands, moreover they can be enact
on the dorsum of extremities, genitalia,
eyelids.
There is no specific grading level and
severity classification for toxicity induced
by As
metal (Pratt et
al. 2016). It
can be acute, sub-acute and chronic.
Severity of As poisoning depends upon the
various elements, which
includes the type
and grade of As
compound, state of valence chemical
compounds, toxic dose, rate of exposure of heavy
metal, duration of exposure and underlying disease illness (Çöl et al.
1999).
PATHOPHYSIOLOGY
After exposure to As, it absorbs in the body and goes to different organs. During transit from blood to tissues, it metabolizes into reactive trivalent arsenite. Trivalent arsenite have ability to bind to sulphahydral group present in keratin filament, skin, hair, nails (Sarma, 2015). After binding to sulphahydral group of proteins, it activates transcription factors, alters the level of growth factors and cytokeratin’s. Due to alteration of cytokeratin’s and p53, As affect differentiation and proliferation of keratinocytes, which are the cells of epidermis (Rossman et al. 2004). In the cells demand of energy, DNA damage and mutation of mitochondria due to As exposure cause differentiation of epidermal keratinocytes. As up-regulates interleukin 1 & 2, beta factors and keratin. Abnormal proliferation of keratinocytes starts to form, and lesions develop in skin, which may coalesce to form hyper pigmented plaques (Palma-Lara et al. 2020). Keratosis mostly occur in areas prone to friction and trauma such as palm of hands and soles of feet. Lesions may develop squamous cell carcinoma (Fig. 1). Abnormal differentiation of keratinocytes, apoptosis and aberrant inflammation cause carcinogenesis. In liver As is methylated into mono-methyl arsenic acid and it is further reduced to mono-methylarsonous acid (Paul et al. 2015). Methylation increases the oxidative stress, this stress cause DNA repair, altered chromosomal abnormalities i.e. sister chromatid changes and gene expression. As acts on P53 compromised cells to cause chromosomal abnormality this cause carcinogenesis of skin (Tao and Wang 2024).
PREVALENCE
The prevalence rates of As keratosis across the
world and countries of South-Asia such as Pakistan, India, Bangladesh, narrative
for the highly polluted domain of the
world due to As
prevalence. Inorganic As has demonstrated
gene amplification, a major potential
finding, since gene amplification of oncogenes has been seen in number of human
tumors with epidemiologic work (Rajiv et al. 2023). Heavy metal poisoning
is interlinked with a number of
occupations. It is directly linked by drinking contaminated tap water, washing
in ground water without any use of filters and potential soil exposure.
A major concern is that the
safe disposal of waste of heavy metals include As, lead, copper, etc. The
concentration of these heavy metals
is higher than the prescribed limit as
set by the United States Food and Drug Administration
and World Health Organization (Somé et al.
2012).
To guarantee compliance
with regulatory limits, quality control measures should be implemented to
monitor metal concentrations. Of the 116 residents surveyed, 81 had clinically
diagnosed As keratosis
and pigmentation changes. Among them were 52 males and 29 females in the age
ranging between 4–82 years (Lonergan et al. 2010). Two cases of squamous
cell carcinoma were detected through skin biopsy in situ. High grades of As in the groundwater and topsoil aided the prevalence of
chronic As poisoning. A revelatory quota of
groundwater in Pakistan is contaminated with As noticed. As contaminated wells
were found around Indus River, suggest that poisoning is due to heavy metal.
The very first noticed and reported
epidemiological case of experimental data based on clinical evidence of As metal causing lesions on skin’s surface and into
deep tissues carried out alongside Indus River (Chakrabarty 2015). A case in
point with cluster of
multi stage survey was conducted and
documented among people (3874) ≥ age of
15 years, is to conclude the prevalence
of arsenicosis,
based on its relation with increasing
level of drinking contaminated groundwater
in urban as well as in rural areas (
population ratio: 1.8 million of
people) in Pakistan due to lack of awareness
programs. Pakistan has low
levels of As metal
exposure
in tap water compared with India,
Philippines, Bangladesh and China. A large population in West of Bengal, India and Uttar Pradesh, susceptible
to inorganic As
through their drinking contaminated water (Singh et
al. 2007). A
survey was conducted involving 7683
study population of all ages in an affected As territory,
noticed skin keratosis, pulmonary effects and pigmentation alterations between
April 1995 and March 1996.
Recently, disease prevalence odd-ratio estimates evidently raised
the sample population who take part in clinical experimental studies and
have had high grades of As in their
sources of drinking contaminated water (≥500 mcg/
L) as compared with such individuals
who had normal skin appearance and exposed to low levels of As (<50 mcg/L) (Table 1).
Such territories are exaggerated
due to the As-rich
sediments grounds
in the Gangetic River of Brahmaputra (Ganga-Jumna)
sink, which flows orderly
millions of years ago (Rahman and Hasegawa 2011; Järup 2003).
DIAGNOSIS
Skin signs are specific for diagnosis. Reports show that
chronic As toxicity affects various bodily systems. Clinical evidence of
chronic As poisoning depends on the dose, exposure duration, and host
vulnerability (Das and Sengupta 2009). It is difficult to diagnose since its
symptoms resemble those of common ailments. As the blood exits quickly, thus
diagnosing long-term exposure necessitates hair or nail testing, which are not
always available. Because trace levels present in food and water, even a
positive test can be difficult to interpret. Many people are unaware they have
been exposed until major health conditions, such as nerve damage or cancer,
arise years later, making diagnosis even more difficult. Concentration of As in
the urine used as an indicator for the exposure of As (Fatmi et al.
2013). Route for the elimination of As from the body is urine. As concentration
in urine has been shown to compare with presence of As in tap water
(groundwater) concentration. As concentration
present in seafood
also affect As measurement in urine.
Organic As have no toxicity on mammals.
If the seafood has been taken from last 2 days then it affects the laboratory
As measures that’s why laboratories only measure inorganic As or its
metabolites. Urine sample should be collected over 24 h time period. More
presence indicates the maximum exposure of As. Typically, human hair and nails
contain higher levels of As than other body parts due to keratin content.
Levels of As
metal in hair give important point of interest which gives meaningful information about
chronic poisoning induced by As
exposure to skin (Singh et al.
2007). There is only a very rough correlation among As concentration in hairs
and As toxicity, which presents a number of challenges for the toxicologist
utilizing this test. Thus, hair concentrations in patients with chronic As
poisoning can range
from 10 parts per million deaths linked to As have been documented to have levels of
about 45 ppm.
Chances of variation of hairs from
inside and outer-side
due to As
content could be significant, which makes results
of a single hair
less accurate
than from larger hair samples. Therefore, samples should be taken from multiple
locations on the head, containing
only one gram of hair clipped near
the area of scalp, the entire sample should be examined (Son et al.
2008; de Luzuriaga et al. 2011). To evaluate toxicity using hair As
concentrations,
contamination outside of the hair should
be eliminated.
The majority of inorganic and organic As in human blood is
removed quite quickly. As in blood will only reflect exposure for a brief
period, making it highly time dependent. Continuous and consistent exposure,
such as drinking water, can lead to steady state As levels in the blood,
allowing for a correlation between As exposure and As blood levels (Vahter
2008; Ali et al. 2013). However, there is no quantitative evidence
linking As exposure to blood As concentrations in humans.
The half-life of As
in the body in comparison to its
half-life in the blood makes it challenging
to determine
the link
between body As
concentrations
and total concentration of As in blood
and organs. The pigmentary and keratotic alterations
observed in arsenicosis can be mimicked by a variety of disorders (Khan et
al. 2015). The study of pathology Hyperkeratosis, parakeratosis,
acanthosis, and papillomatosis are epidermal alterations associated with As
keratosis (Fig. 1). Basal pigmentation and
dysplastic alterations are also infrequently observed. Both benign and
malignant forms of arsenical hyperkeratosis are distinguished by the presence
or lack of cellular atypia. There are no distinct histological characteristics
that distinguish As-induced cutaneous cancers from their non-As-induced
counterparts. Diagnostics in laboratories, the primary method of determining
the environmental burden is to test the amounts (Ahamed et al. 2006;
Ghosh 2013).
In China, As poisoning was commonly treated using As removal agents i.e. sodium thiosulphate and Dimercaptopropyl sulfonate. Concentration of As in blood and urine were reduced after these drugs were given to 18 (43.90%) patients who were cancer free and 6 (14.6%) patients who were cancerous (Camaclang et al. 2019). Two patients received sodium thiosulphate noticed a drop in blood As levels, whereas 4 patients received dimercaptopropyl sulfonate saw their levels return to normal. Following treatment with dimercaptopropyl sulfonate, two cancer patients had higher urine As levels (Balali-Mood et al. 2025; Islam et al. 2025).
Leaves of Drumstick tree (Moringa oleifera) and leaves of spinach (Ipomea aquatica) and the raised parts of
them,
had increased effects in the toxicity due to As. Silybum marianum, Garlic (
Allium sativum), Turmeric (Curcuma longa),
and some algae along with fibers was the
most beneficial herbs
for the intoxication treatment due to As. Chelating agents work by attaching themselves to
the metal ion, making it more soluble in water and facilitate quicker kidney
elimination. As a result, it lowers the body’s total As load and lowers the
risk of cancer (Verma et al. 2025; Zahra et al. 2025). The clearance of skin lesions is accelerated by
keratolytic treatment like 20% of
urea and 6–10% of salicylic acid in combination
with agents which forms chelates and complex compound formulation. Retinoid have anti-keratinizing
properties, their therapy has been utilized to treat As keratosis. By
influencing
the gene expression, which may impact
cell distinction, proliferation,
multiplication and induction of apoptosis, they
also aid in the chemo-prevention of malignancies linked to As (Ullah et al.
2024). Drinking contaminated groundwater tanned with As, people who take a high
calorie, antioxidants rich meals had lessened effects of As toxicity (Das and
Sengupta 2009). Numerous studies have demonstrated that
polyphenols, black tea and leaves of
green tea, Vitamin A (Retinol), Vitamin C (Ascorbic acid), Vitamin E (Tocopherol)
all reduced the effects of As toxicity. After six weeks of topical treatment
with 5% imiquimod cream once daily, the neoplasms completely resolved clinically and didn’t reappear
throughout more than three years of clinical observation. In order to identify
and eradicate cancer cell, it activates immune cells like T-cells and dendritic
cells (Tang et al. 2023).
PREVENTION STRATEGIES
Prevention is the core step in lowering chronic As toxicity. The best way is the prevention rather to cure. The health impacts and prevention of As have been the attention of many nations. Acknowledge the severity of the arsenicosis epidemic, which affects a sizable portion of the global population and for which there is currently no cure (Rajiv et al. 2023). Increased prevention measures are of importance to us because to the substantial impact on the population at risk as well as the additional conditions linked to ongoing drinking water exposure to As. Filtration is the most used clean up method (Hye 2018). SONO filters, iron filters, membrane filters and nanoparticle filters are the common techniques used to remove the As from water. Different filters work better at different water pH level. It is important to understand that As cannot be removed by boiling the water (Tao and Wang 2024). It offers a promising solution for removing As from water and soil. It is the natural and cheap way to remove As. Plants can remove As regardless of water pH, it clears the contaminated area of As. In reality, these plants are hyper accumulating (Hassan 2018). It doesn’t eliminate contaminations from polluted areas instead, it reduces the contaminated mobility, As which prevents plants from absorbing it. As can be absorbed by certain hyper accumulating plants, which then move it to their aerial parts and release it into the atmosphere as arsine (Saha 2003). This should not be attempted form an environmental perspective. Using plant metabolism, this is a combination of phytodegradation and phytostabilization. As is absorbed by hyper accumulating plants in watery environments (Shajil et al. 2024).
CONCLUSION
As keratosis can cause variable incorporations. Its
prevalent
nature and their huge presence
globally, makes it a difficult chore to prevent these aspects
of
poisoning.
The outcome of this experimental study
and limited research on keratosis revealed that the contemporary prevalence of
skin lesions caused by As in the community was
2.21%. Moreover,
beside the cases of arsenicosis, the
primarily clinical manifestation was keratosis, which is then followed by
hyperpigmentation and then comes the hyperkeratosis,
were observed.
There must be checkpoints to evaluate
the As exposure and related poisoning in
between the population in the area under-study by using body biomarkers. A global epidemic, global agencies i.e. World Health
Organizations
and the UNEP (United Nations
Environment Program) can help the communities by encouraging
hyperawareness, and the surroundings
global etiquette
for acceptable limits of As exposure in periodic
history.
People who are affected by these heavy
metals and have had previously
developed history of keratosis should
must pay attention to
decrease
improbability of malignant modification
and they must hold identical preventive
steps. Lesions are cancerous in nature
and these cancerous cells may invade into other body tissues and can also cause
damage to them, so they should be closely monitored, and surgical treatment
strategies should be followed and implemented to
affected individuals.
AUTHOR CONTRIBUTIONS
NUA: Topic decision in publication, Journal approach, publication process, data defining, writing and data collection; HK: Introduction to Arsenic, Heavy metal poisoning, Prevalence; ZB Intervention traditional and modern strategies; AZ: Abstract and diagnosis; KA: Introduction to arsenic keratosis and conclusion; RK Pathophysiology; HS: Diagnosis; ZS: Pathophysiology; RI: Intervention traditional and modern strategies; MY: Introduction to arsenic keratosis and conclusion, data collection and in writing.
CONFLICTS OF INTEREST
No conflict of interest among the authors to declare
DATA AVAILABILITY
Not applicable to this paper
ETHICS APPROVAL
Not applicable to this paper.
FUNDING SOURCE
Not applicable to this paper.
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